Abstract This is an application for a K23 award for Dr. Bhupesh Panwar, Assistant Professor in the Division of Nephrology at the University of Alabama at Birmingham. Dr. Panwar is a clinical investigator with a research focus on the interactions between disturbed iron and mineral metabolism related to kidney disease. This award will provide Dr. Panwar the support necessary to become skilled in patient-oriented clinical and translational research in individuals with chronic kidney disease (CKD). To achieve these goals Dr. Panwar has assembled a team of mentors with a wealth of clinical and translational research experience and a track-record in mentoring junior investigators. When this is combined with the exceptional resources, institutional support, and the proposed career development activities, Dr. Panwar will be well positioned to achieve his long-term goal. Fibroblast growth factor 23 (FGF23) is a key regulator of phosphorus and vitamin D metabolism. An elevation in circulating FGF23 is among the earliest manifestations of disturbed mineral homeostasis in CKD. However, factors that stimulate the increase in FGF23 early in the course of CKD are unclear. Identification of these factors could lead to development of novel therapeutics to reduce FGF23 levels in CKD. This is important in that elevated FGF23 is a strong predictor of increased cardiovascular mortality and morbidity in CKD. Iron deficiency has been shown to stimulate FGF23 via stabilization of hypoxia-inducible factor (HIF) 1?, suggesting that correcting iron deficiency in early CKD could be one potential strategy to reduce FGF23 levels in CKD. Converging lines of evidence also suggest that FGF23 can regulate iron bioavailability by modulating the secretion of hepcidin, the central hormone controlling iron homeostasis. However, to date, few studies examined the effects of iron supplementation on FGF23 secretion and conversely, of lowering FGF23 on iron bioavailability in CKD patients. In addition, although hypoxia is a powerful stimulant of HIF1?, no studies have examined whether treating hypoxia lowers FGF23 levels in CKD patients. The current proposal will establish the physiological relevance of these proposed shared pathways by (1) examining the effect of iron infusion on FGF23 levels in individuals with or without CKD (Aim 1.1); (2) determining if lowering of FGF23 would improve iron bioavailability by reducing hepcidin (Aim 1.2); and (3) determining whether correction of hypoxia in CKD patients reduces FGF23 levels (Aim 2). This innovative proposal uses multiple approaches to elucidate the cross-talk between FGF23, iron and hypoxia in CKD patients, with the ultimate goal of identifying novel potential therapeutic targets for improving outcomes in CKD patients. Importantly, findings from these studies will provide the foundation for a future R01 application for Dr. Panwar.